ABSTRACT
In collaboration with the American College of Veterinary Radiology.
Subject(s)
Dog Diseases/diagnosis , Gastric Dilatation/veterinary , Intestinal Volvulus/veterinary , Animals , Dog Diseases/diagnostic imaging , Dog Diseases/therapy , Dogs , Gastric Dilatation/diagnosis , Gastric Dilatation/diagnostic imaging , Gastric Dilatation/therapy , Intestinal Volvulus/diagnosis , Intestinal Volvulus/diagnostic imaging , Intestinal Volvulus/therapy , Male , RadiographyABSTRACT
In this study, we aimed to validate the feasibility of receptor-targeted tumor theranostics with folate-conjugated (FA) and camptothecin-loaded (CPT) acoustic nanodroplets (NDs) (collectively termed FA-CPT-NDs). The ND formulation was based on lipid-stabilized low-boiling perfluorocarbon that can undergo acoustic droplet vaporization (ADV) under ultrasound (US) exposure. Conjugation of folate enhanced the selective delivery to tumors expressing high levels of folate receptor (FR) under mediation by the enhanced permeability and retention effect. In vitro and in vivo studies were performed using FR-positive KB and FR-negative HT-1080 cell lines and mouse xenograft tumor models. Simultaneous therapy and imaging were conducted with a clinical US imaging system at mechanical indices of up to 1.4 at a center frequency of 10 MHz. The results demonstrated that FA-CPT-NDs selectively attached to KB cells, but not HT-1080 cells. The targeted ADV caused instant and delayed damage via mechanical disruption and chemical toxicity to decrease the viability of KB cells by up to 45%, a much higher decrease than that achieved by the NDs without folate conjugation. The in vivo experiments showed that FR-mediated targeting successfully enhanced the EPR of FA-CPT-NDs in KB tumors mainly on the tumor periphery as indicated by immunofluorescence microscopy and US B-mode imaging. Treatments with FA-CPT-NDs at a CPT dose of 50 µg/kg inhibited the growth of KB tumors for up to six weeks, whereas treatment with NDs lacking folate produced a 4.6-fold increase in tumor volume. For HT-1080 tumors, neither the treatments with FA-CPT-NDs nor those with the NDs lacking folate presented tumor growth inhibition. In summary, FR-targeted tumor theranostics has been successfully implemented with FA-CPT-NDs and a clinical US unit. The ligand-directed and EPR-mediated accumulation provides active and passive targeting capabilities, permitting the antitumor effects of FA-CPT-NDs to be exerted selectively to FR-positive tumors and simultaneously providing targeted US imaging capabilities.
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Camptothecin/administration & dosage , Folic Acid/chemistry , Nanostructures , Neoplasms/drug therapy , Theranostic Nanomedicine , Xenograft Model Antitumor Assays , Animals , Antineoplastic Agents, Phytogenic/therapeutic use , Camptothecin/therapeutic use , Cell Line, Tumor , Humans , Male , Mice , Mice, Inbred NOD , Mice, SCIDABSTRACT
A lipid-polymer composite structure was developed for tuning of inertial cavitation activity of microbubbles under ultrasound exposure. The incorporation of a thin layer of polymer networks inside the lipid monolayer resulted in marked reduction in the inertial cavitation dose. This strategy has the potential to increase the safety of ultrasound theranostic applications assisted by microbubble cavitation.
ABSTRACT
Atlantoaxial (AA) subluxation is an uncommon disorder that can cause various degrees of neurological deficits in dogs. Block vertebra is a congenital deformation involving the fusion of two or more vertebrae. This report describes two dogs with cervical block vertebrae from C(2) to C(5) and C(2) to C(4), respectively. We hypothesize that the fused cervical vertebrae created a "fulcrum effect" at the AA joint and predisposed these dogs to traumatic AA subluxation.
